Nociceptive information associated with myocardial ishemia is transmitted to the brain by spinothalamic and spinoreticular pathways. This research will determine how thoracic spinal neurons that project to higher centers respond to bradykinin and other algesic chemicals applied to the heart. The upper thoracic spinal cord of cats and monkeys will be explored with glass of metal microelectrodes to locate cells that project the thalamus or reticular formation. These responses will also be compared with those to somatic nociceptive stimuli and to coronary artery occlusion, since these cells are the place for convergence of referred pain, a common occurrence in agina pectoris. In addition to responding to both visceral and somatic sensory input, these neurons are often inhibited and sometimes excited by vagal afferent activity that descends from the brain stem. The source of vagal afferent activity will be studied by stimulating various branches of the vagus nerve, and the types of fibers conducting this activity will be tested by differential stimulating and blocking techniques. The nature of the inhibition will be shown by measuring the time course of interaction between excitatory nociceptive stimuli and descending vagal inhibition. Finally, focal stimulation in the brain stem will begin to show the pathways in the brain stem involved in this descending control system. This project will contribute to understanding of cardiac pain and its possible modification by other visceral and somatic sensory inputs, especially this newly discovered vagal afferent descending control system.